HIV InfectionsPhase 2NCT00125983
Drug Interactions Between Lopinavir/Ritonavir and Oral or Patch Contraceptives in HIV Infected Women
A Phase 2 study testing Lopinavir/ritonavir, Ortho Novum 1/35 and Ortho Evra in people with HIV Infections and Pregnancy, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 sites in 2 countries.
Trial summary
The purpose of this study is to examine the drug interactions between a protease inhibitor (PI)-based regimen including lopinavir/ritonavir (LPV/r) and two forms of contraceptive medications in HIV infected women. Read more about this study
- Who is it for?
- Ages 13 years and older, women only
- Conditions the study is for
- HIV Infections, Pregnancy
- What is being tested?
- Lopinavir/ritonavir, Ortho Novum 1/35 and Ortho Evra
- How many people
- 32 participants
- Where
- 9 sitesin 2 countries
- Study dates
- Start not givento Jan 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 years and older
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- HIV infected
- CD4 count of 200 cells/mm3 or more within 45 days of study entry
- HIV-1 RNA viral load less than 55,000 copies/ml within 45 days of study entry
- Parent or guardian willing to provide informed consent
- Negative pregnancy test within 45 days of study entry
- Willing to use acceptable forms of contraception
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- Agrees not to change current smoking or non-smoking habits
- Agrees not to consume caffeine on Day 1, Days 17 through 19, and Day 24 until after the last blood sample of that day is drawn
- Agrees not to consume alcohol within 48 hours of PK sampling periods
- Patients on methadone maintenance therapy should be on a stable methadone dose for at least 60 days prior to study entry and continue maintenance therapy throughout the study
- Have taken LPV/r for at least 60 consecutive days prior to study entry and taken the same dose twice daily for at least 14 days prior to study entry. Women switching from capsule formulation LPV/r to new tablet formulation of 200mg/50 mg LPV/r must be taking twice-daily doses of this formulation, for a total daily dose of 800 mg/200 mg LPV/r, for at least 7 days prior to study entry.
- Have not taken or currently not taking a PI- or non-nucleoside reverse transcriptase inhibitors (NNRTI-) based regimen for at least 30 days prior to study entry, and not planning on starting PIs or NNRTIs during the 6-week study period. Women who have not been on HAART for at least 30 days prior to study entry are also eligible.
- For patients not receiving HAART, documentation that they have been counseled about the benefits of HIV treatment within 90 days of study entry and have elected not to initiate therapy
Who cannot join
- Use of systemic hormonal therapies containing estrogens, progestins, or anabolic steroids (e.g., estrogen, progesterone, oral contraceptives, Mirena [levonorgestrol] intrauterine device [IUD], Progestasert [progesterone] IUD) within 60 days of study entry
- Anabolic therapies (nandrolone decanoate or megestrol) within 60 days of study entry
- Systemic glucocorticoids within 14 days of study entry
- Certain medical conditions. More information on this criterion can be found in the protocol.
- Need for prolonged bedrest after major surgery
- Smokers of ages 35 or older
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- NNRTIs within 30 days of study entry
- Nausea, vomiting, or abdominal pain of Grade 3 or higher within 30 days of study entry
- Known allergy or sensitivity to ethinyl estradiol (EE), norelgestromin (NGMN), or components of the Ortho Evra contraceptive patch
- Known allergy or sensitivity to norethindrone or components of the ON 1/35 oral contraceptive pill
- Serious illness requiring systemic treatment or hospitalization within 14 days of study entry
- Undiagnosed abnormal vaginal bleeding
- Depo-Provera (medroxyprogesterone acetate) within 180 days of study entry
- Lunelle (estradiol cypionate and medroxyprogesterone acetate) within 90 days of study entry
- Use of certain medications within 30 days of study entry
- Current drug or alcohol use or dependence that, in the opinion of the investigator, may interfere with the study
- Unable to adhere to HAART, the Ortho Evra contraceptive patch, or single dose ON 1/35 regimens
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United States8 sites
University of Colorado Hospital CRS
Aurora, Colorado
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, 96816-2396
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, 46202-5250
USC CRS
Los Angeles, California, 90033-1079
Usc La Nichd Crs
Los Angeles, California, 90033
Beth Israel Med. Ctr., ACTU
New York, New York, 10003
Weill Med. College of Cornell Univ., The Cornell CTU
New York, New York, 10021
Pitt CRS
Pittsburgh, Pennsylvania
About this study
Official title: A Phase II Pharmacokinetic Study of the Transdermal Contraceptive System and Oral Contraceptive in HIV-1 Infected Women on Lopinavir/Ritonavir
The purpose of this study is to examine the drug interactions between a protease inhibitor (PI)-based regimen including lopinavir/ritonavir (LPV/r) and two forms of contraceptive medications in HIV infected women.
Read the detailed description
Both PIs and oral contraceptives are metabolized by the same pathway, which significantly decreases the effectiveness of oral contraceptives and limits the contraceptive choices available to HIV infected women. More effective hormonal contraceptive methods are necessary for preventing unintended pregnancy in women taking highly active antiretroviral therapy (HAART). Ortho Evra is a contraceptive patch that was approved by the FDA in 2001; it uses a transdermal contraceptive system, and higher rates of compliance have been associated with its use, compared to oral contraceptives. Because Ortho Evra is administered as a contraceptive patch worn on the skin, it may bypass the metabolic pathway common to both PIs and oral contraceptives, making it a viable contraceptive option for HIV infected women on PI-based regimens. The purpose of the study is to examine the interaction between a PI-based regimen containing LPV/r and two forms of contraceptive medications, Ortho Evra and an oral contraceptive, Ortho Novum (ON 1/35), in HIV infected women.
Participants will be enrolled in this study for 6 weeks and will be assigned to one of two study arms, depending on their HAART regimen at study entry. Participants in both arms will also be stratified by age. Arm A participants will receive 400 mg/100 mg LPV/r twice daily along with two or more nucleoside reverse transcriptase inhibitors (NRTIs). Arm B participants will receive a regimen containing only NRTIs or no HAART. HAART will not be provided by this study. All patients will receive a single dose of ON 1/35 on Day 1 and will start the Ortho Evra contraceptive patch on Day 3. A physical exam, pap smear, pregnancy test, viral load test, CD4 and CD8 counts, and blood collection will occur at or before study entry and on Day 24. Pharmacokinetic analyses will occur on Days 1 through 3, 17 through 19, and 24.
- Conditions
- HIV Infections, Pregnancy
- Being tested
- Lopinavir/ritonavir, Ortho Novum 1/35, Ortho Evra
- Keywords
- Birth Control Pills, Oral Contraceptives, Contraceptive Patch, Pharmacokinetics, Antiretroviral Therapy, Highly Active, Protease Inhibitor, Treatment Experienced, Treatment Naive, Contraception
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lopinavir/ritonavirDrug
Ortho Novum 1/35Drug
Ortho EvraDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Days 17, 18, 19, and 24 Ortho Evra transdermal contraceptive ethinyl estradiol (EE) area under the concentration-time curve (AUC)
Secondary outcomes (6)
Intensive EE AUC pharmacokinetics (PK) after single dose Ortho Novum (ON) 1/35 and after Ortho Evra administration on Days 17, 18, 19, and 24
Day 1 intensive EE AUC PK after single dose ON 1/35
Days 17, 18, 19, and 24 norelgestromin (NGMN) AUC
changes in HIV RNA viral load, CD4 and CD8 counts and their respective percentages, sex hormone binding globulin levels, and liver enzymes from baseline to Days 17, 18, 19, and 24
occurrence of nausea and vomiting, breast tenderness, headache, skin irritation, vaginal bleeding, change in weight, change in blood pressure, change in appetite, mood changes, vaginal infection, and gallbladder disease
PK parameters of LPV in Arm A at baseline and on Days 17, 18, 19, and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2005 (estimated)
- Study completionJan 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Responsible party
- Sponsor
- Investigators
- Lori Kamemoto, MD, MPH, Study chair, Hawaii AIDS Clinical Research Program, University of Hawaii School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00125983
- Sponsor's protocol ID
- A5188
- Other IDs
- 10011, AACTG A5188
- Status last verified
- Oct 2021
- First submitted
- 29 Jul 2005
- Last updated
- 1 Nov 2021
- Results posted
- No
Publications
Mildvan D, Yarrish R, Marshak A, Hutman HW, McDonough M, Lamson M, Robinson P. Pharmacokinetic interaction between nevirapine and ethinyl estradiol/norethindrone when administered concurrently to HIV-infected women. J Acquir Immune Defic Syndr. 2002 Apr 15;29(5):471-7. doi: 10.1097/00126334-200204150-00007.
PubMed 11981363Ouellet D, Hsu A, Qian J, Locke CS, Eason CJ, Cavanaugh JH, Leonard JM, Granneman GR. Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers. Br J Clin Pharmacol. 1998 Aug;46(2):111-6. doi: 10.1046/j.1365-2125.1998.00749.x.
PubMed 9723818Audet MC, Moreau M, Koltun WD, Waldbaum AS, Shangold G, Fisher AC, Creasy GW; ORTHO EVRA/EVRA 004 Study Group. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: a randomized controlled trial. JAMA. 2001 May 9;285(18):2347-54. doi: 10.1001/jama.285.18.2347.
PubMed 11343482Vogler MA, Patterson K, Kamemoto L, Park JG, Watts H, Aweeka F, Klingman KL, Cohn SE. Contraceptive efficacy of oral and transdermal hormones when co-administered with protease inhibitors in HIV-1-infected women: pharmacokinetic results of ACTG trial A5188. J Acquir Immune Defic Syndr. 2010 Dec;55(4):473-82. doi: 10.1097/QAI.0b013e3181eb5ff5.
PubMed 20842042
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Pharmacokinetic Study of the Transdermal Contraceptive System and Oral Contraceptive in HIV-1 Infected Women on Lopinavir/Ritonavir
- ClinicalTrials.gov ID
- NCT00125983
- Acronym / sponsor ID
- A5188
- Conditions
- HIV Infections, Pregnancy
- Keywords
- Birth Control Pills, Oral Contraceptives, Contraceptive Patch, Pharmacokinetics, Antiretroviral Therapy, Highly Active, Protease Inhibitor, Treatment Experienced, Treatment Naive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Study completion
- Jan 2007 (actual)
- First posted
- 2 Aug 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to examine the drug interactions between a protease inhibitor (PI)-based regimen including lopinavir/ritonavir (LPV/r) and two forms of contraceptive medications in HIV infected women.
Detailed description
Both PIs and oral contraceptives are metabolized by the same pathway, which significantly decreases the effectiveness of oral contraceptives and limits the contraceptive choices available to HIV infected women. More effective hormonal contraceptive methods are necessary for preventing unintended pregnancy in women taking highly active antiretroviral therapy (HAART). Ortho Evra is a contraceptive patch that was approved by the FDA in 2001; it uses a transdermal contraceptive system, and higher rates of compliance have been associated with its use, compared to oral contraceptives. Because Ortho Evra is administered as a contraceptive patch worn on the skin, it may bypass the metabolic pathway common to both PIs and oral contraceptives, making it a viable contraceptive option for HIV infected women on PI-based regimens. The purpose of the study is to examine the interaction between a PI-based regimen containing LPV/r and two forms of contraceptive medications, Ortho Evra and an oral contraceptive, Ortho Novum (ON 1/35), in HIV infected women.
Participants will be enrolled in this study for 6 weeks and will be assigned to one of two study arms, depending on their HAART regimen at study entry. Participants in both arms will also be stratified by age. Arm A participants will receive 400 mg/100 mg LPV/r twice daily along with two or more nucleoside reverse transcriptase inhibitors (NRTIs). Arm B participants will receive a regimen containing only NRTIs or no HAART. HAART will not be provided by this study. All patients will receive a single dose of ON 1/35 on Day 1 and will start the Ortho Evra contraceptive patch on Day 3. A physical exam, pap smear, pregnancy test, viral load test, CD4 and CD8 counts, and blood collection will occur at or before study entry and on Day 24. Pharmacokinetic analyses will occur on Days 1 through 3, 17 through 19, and 24.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 13 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- HIV infected
- CD4 count of 200 cells/mm3 or more within 45 days of study entry
- HIV-1 RNA viral load less than 55,000 copies/ml within 45 days of study entry
- Parent or guardian willing to provide informed consent
- Negative pregnancy test within 45 days of study entry
Key exclusion criteria (17 listed)
- Use of systemic hormonal therapies containing estrogens, progestins, or anabolic steroids (e.g., estrogen, progesterone, oral contraceptives, Mirena [levonorgestrol] intrauterine device [IUD], Progestasert [progesterone] IUD) within 60 days of study entry
- Anabolic therapies (nandrolone decanoate or megestrol) within 60 days of study entry
- Systemic glucocorticoids within 14 days of study entry
- Certain medical conditions. More information on this criterion can be found in the protocol.
- Need for prolonged bedrest after major surgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lopinavir/ritonavir | Drug | – |
| Ortho Novum 1/35 | Drug | – |
| Ortho Evra | Drug | – |
Primary outcome
Days 17, 18, 19, and 24 Ortho Evra transdermal contraceptive ethinyl estradiol (EE) area under the concentration-time curve (AUC)
6 secondary outcomes
Intensive EE AUC pharmacokinetics (PK) after single dose Ortho Novum (ON) 1/35 and after Ortho Evra administration on Days 17, 18, 19, and 24
Day 1 intensive EE AUC PK after single dose ON 1/35
Days 17, 18, 19, and 24 norelgestromin (NGMN) AUC
changes in HIV RNA viral load, CD4 and CD8 counts and their respective percentages, sex hormone binding globulin levels, and liver enzymes from baseline to Days 17, 18, 19, and 24
occurrence of nausea and vomiting, breast tenderness, headache, skin irritation, vaginal bleeding, change in weight, change in blood pressure, change in appetite, mood changes, vaginal infection, and gallbladder disease
PK parameters of LPV in Arm A at baseline and on Days 17, 18, 19, and 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2021.
- Background: PubMed 11981363Mildvan D, Yarrish R, Marshak A, Hutman HW, McDonough M, Lamson M, Robinson P. Pharmacokinetic interaction between nevirapine and ethinyl estradiol/norethindrone when administered concurrently to HIV-infected women. J Acquir Immune Defic Syndr. 2002 Apr 15;29(5):471-7. doi: 10.1097/00126334-200204150-00007.
- Background: PubMed 9723818Ouellet D, Hsu A, Qian J, Locke CS, Eason CJ, Cavanaugh JH, Leonard JM, Granneman GR. Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers. Br J Clin Pharmacol. 1998 Aug;46(2):111-6. doi: 10.1046/j.1365-2125.1998.00749.x.
- Background: PubMed 11343482Audet MC, Moreau M, Koltun WD, Waldbaum AS, Shangold G, Fisher AC, Creasy GW; ORTHO EVRA/EVRA 004 Study Group. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: a randomized controlled trial. JAMA. 2001 May 9;285(18):2347-54. doi: 10.1001/jama.285.18.2347.
- Results publication: PubMed 20842042Vogler MA, Patterson K, Kamemoto L, Park JG, Watts H, Aweeka F, Klingman KL, Cohn SE. Contraceptive efficacy of oral and transdermal hormones when co-administered with protease inhibitors in HIV-1-infected women: pharmacokinetic results of ACTG trial A5188. J Acquir Immune Defic Syndr. 2010 Dec;55(4):473-82. doi: 10.1097/QAI.0b013e3181eb5ff5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lori Kamemoto, MD, MPH study chair
Hawaii AIDS Clinical Research Program, University of Hawaii School of Medicine
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lopinavir/ritonavir, Ortho Novum 1/35 and Ortho Evra in people with HIV Infections and Pregnancy, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Days 17, 18, 19, and 24 Ortho Evra transdermal contraceptive ethinyl estradiol (EE) area under the concentration-time curve (AUC). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00125983, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.